Nkg7, or natural killer cell granule protein-7, is a cytolytic granule-associated molecule expressed in cytotoxic lymphocytes, including CD8+ T cells and natural killer (NK) cells. It plays a crucial role in the cytotoxic function of these cells, regulating processes such as cytolytic granule exocytosis, which is essential for eliminating malignant cells. It may also be involved in regulating endosomal vesicle trafficking [4,5].

In Nkg7-deficient mice, neoantigen-expressing tumors grow faster, indicating a key role of Nkg7 in controlling intratumor T-cell accumulation and activation. Nkg7 is upregulated on intratumor antigen-specific CD8+ T cells and NK cells and is required for T-cell accumulation in the tumor microenvironment [2]. Deletion of Nkg7 reduces the ability of CD8+ T cells to degranulate and kill target cells in vitro, but also leads to a prolonged immune synapse with tumor cells and increased secretion of inflammatory cytokines [3].

In conclusion, Nkg7 is essential for the cytotoxic function of CD8+ T cells and NK cells, and plays a significant role in antitumor immunity. Gene-knockout mouse models have revealed its importance in controlling tumor growth and T-cell accumulation in the tumor microenvironment, providing insights into its potential as a therapeutic target for enhancing cancer immunotherapy [1,2].

References:

1. Wen, Ti, Barham, Whitney, Li, Ying, Billadeau, Daniel D, Dong, Haidong. 2021. NKG7 Is a T-cell-Intrinsic Therapeutic Target for Improving Antitumor Cytotoxicity and Cancer Immunotherapy. In Cancer immunology research, 10, 162-181. doi:10.1158/2326-6066.CIR-21-0539. https://pubmed.ncbi.nlm.nih.gov/34911739/

2. Li, Xian-Yang, Corvino, Dillon, Nowlan, Bianca, Smyth, Mark J, Engwerda, Christian R. 2022. NKG7 Is Required for Optimal Antitumor T-cell Immunity. In Cancer immunology research, 10, 154-161. doi:10.1158/2326-6066.CIR-20-0649. https://pubmed.ncbi.nlm.nih.gov/35013002/

3. Lelliott, Emily J, Ramsbottom, Kelly M, Dowling, Mark R, Brennan, Amelia J, Oliaro, Jane. 2022. NKG7 Enhances CD8+ T Cell Synapse Efficiency to Limit Inflammation. In Frontiers in immunology, 13, 931630. doi:10.3389/fimmu.2022.931630. https://pubmed.ncbi.nlm.nih.gov/35874669/

4. Schuster, Iona S, Andoniou, Christopher E. 2020. NKG7 - regulating endosomal pathways? In Immunology and cell biology, 98, 802-804. doi:10.1111/imcb.12403. https://pubmed.ncbi.nlm.nih.gov/33016375/

5. Ng, Susanna S, De Labastida Rivera, Fabian, Yan, Juming, Smyth, Mark J, Engwerda, Christian R. 2020. The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation. In Nature immunology, 21, 1205-1218. doi:10.1038/s41590-020-0758-6. https://pubmed.ncbi.nlm.nih.gov/32839608/